Neutralizing autoantibody against factor XIII A subunit resulted in severe bleeding diathesis with a fatal outcome – characterization of the antibody

Essentials Autoantibody against factor XIII (FXIII) is a rare but severe acquired hemorrhagic diathesis. In an elderly patient, anti‐FXIII‐A antibody led to severe bleedings with fatal outcome. The neutralizing autoantibody bound to FXIII with high affinity (Ka≈10 9 m ‐1 ). The dominant effect of the autoantibody was the inhibition of activated FXIII.Summary Autoantibodies may develop against the catalytic A subunit of factor XIII ( FXIII ‐A) or the carrier B subunit ( FXIII ‐B). Autoimmune FXIII ‐A deficiency was diagnosed in an elderly (75 years) patient with severe bleeding symptoms. The patient had 3% FXIII activity, and unmeasurable FXIII ‐A 2 B 2 and FXIII ‐A antigens in the plasma, whereas, in the platelet lysate, activity and FXIII ‐A antigen values were normal. As revealed by western blotting, FXIII antigen was present in the plasma, but the autoantibody interfered with the immunoassays. A mixing study indicated the presence of inhibitor with a titer of 63.2 Bethesda units ( BU ). The patient's IgG bound to FXIII ‐A 2 B 2 and to FXIII ‐A 2 with equally high affinity ( K a in the range of 10 9 m −1 ). It exerted a multiple inhibitory effect on FXIII activation/activity ( IC 50: 50 μg mL −1 ). Immunosupressive therapy gradually decreased the autoantibody titer to 8.0 BU , but FXIII activity remained very low, and, owing to recurrent bleeding, the patient died.